Case Studies In Small Animal
Text from "Small Animal Cardiovascular Medicine"
In 1986-87, one of the authors (MDK) and others discovered that taurine deficiency was the primary cause of DCM in cats. Since this discovery, the proper name for this disease should be taurine deficiency-induced myocardial failure. Because this name is cumbersome, the disease is still commonly called feline DCM although not all cases of feline DCM are due to taurine deficiency.
Taurine is a sulfur containing amino acid first isolated from ox bile. One of its function is to conjugate bile acids, along with glycine in some species. Although it is an amino acid, it is not a constituent of proteins. Its definitive role in cellular function is not known but it is concentrated in the cytoplasm up to 250 times that in plasma. This concentration is maintained by active transport and is modulated by β-adrenergic receptors. The highest cellular concentration is found in excitable tissue such as myocardium, retina, central nervous system, and skeletal muscle. It is also present in a high concentration in leukocytes and platelets. In the heart, taurine has been postulated to help modulate intracellular osmolality, calcium concentration, and transmembrane ion fluxes.
In a study reported in 1987, all cases of DCM in cats presented to our hospital (the UC-Davis Veterinary Medical Teaching Hospital) were taurine-deficient. In addition, echocardiographic measures of cardiac function returned either to normal or close to normal following 2-3 months of taurine supplementation. Following this discovery, it was quickly discovered that the source of the taurine deficiency was nutritional. Dry cat foods contained too little taurine while the taurine in canned foods was not biologically available in adequate amounts. This was quickly remedied by the cat food manufacturing industry adding more taurine to their dietary formulations. Subsequently the prevalence of feline DCM decreased to <10% of pre-1987 levels. All these facts are compatible with the theory that taurine is the only factor responsible for feline DCM. However, when experimental cats are fed taurine deficient diets and are made systemically deficient, only about 30% develop echocardiographic evidence of myocardial failure. This suggests some other factor or factors may also be involved. It is interesting that cats that develop myocardial failure on a taurine-deficient diet, will redevelop myocardial failure if they are first treated with taurine to restore myocardial function and then redepleted of taurine. Cats that do not develop myocardial failure the first time do not subsequently develop it. This suggests something unique about individual cats and their sensitivity to taurine deficiency. One study has suggested that a genetic factor may be involved. Since the disease has all but disappeared, interest in additional research has decreased markedly. Consequently, the other factor or factors involved may never be identified.
Cats are obligate carnivores with an absolute dietary requirement of taurine. Taurine is not an essential amino acid in dogs (i.e., they can maintain a normal plasma concentration without dietary intake). However, taurine deficiency is occasionally associated with DCM in dogs. In one report, plasma taurine concentration was low in 17% of the 75 dogs with DCM studied. Plasma taurine concentration was not decreased in the breeds that are more commonly afflicted with DCM. Instead, all of the American cocker spaniels, three of the five golden retrievers, and four of the seven atypical or mixed breeds with DCM in this study had a low plasma taurine concentration. The first two American cocker spaniels treated with taurine supplementation, however, did not respond. L-carnitine was supplemented along with taurine in the next two American cocker spaniels with DCM and both dogs responded although plasma carnitine concentration was not decreased in these dogs. Following this, a clinical trial examining exclusively American cocker spaniels was completed. This study found all 11 American cocker spaniels to be systemically taurine-deficient. Echocardiographic measures of myocardial performance improved, the dogs clinically improved, and cardiovascular drug support could be removed 3-4 months after starting supplementation with taurine and carnitine. Consequently, it is now known that American cocker spaniels with DCM are taurine-deficient and it is assumed that the taurine deficiency is at least a part of the etiology of the disease in this breed. Exactly how L-carnitine is related to the disease in this breed is unknown. We have documented echocardiographic improvement in some dogs with only taurine supplementation so carnitine may not be involved at all. Exactly why American cocker spaniels are systemically taurine deficient is unknown. We have examined renal clearance of taurine in one American cocker spaniel with DCM and a very low plasma taurine concentration. The urine concentration was also extremely low, suggesting that excess renal excretion of taurine is not the underlying abnormality in this breed. However, the fractional excretion of taurine in this dog was modestly increased.
Although taurine is not an essential amino acid in dogs, we have noted systemic taurine deficiency occasionally in dogs fed vegetarian diets. One situation involved a household where two dogs were fed tofu and brown rice exclusively. Both dogs had DCM and a low plasma taurine concentration. One dog died before supplementation could improve its myocardial function. The other dog improved.
Only about 30% of cats that are taurine-deficient develop echocardiographic evidence of myocardial failure. Of the cats with myocardial failure, about 30% develop severe myocardial failure (shortening fraction <15%). Cats with severe myocardial failure are often stable for months to years. Some of these cats appear to develop heart failure suddenly. More likely they develop heart failure more slowly and then reach a critical point. Consequently, they only appear to have an acute onset of heart failure.
Before the discovery that taurine was the cause of DCM in cats, the prognosis for survival in these cats was poor to grave. They usually presented with severe congestive heart failure and severe low-output heart failure. Survival time was hours to a few months. Taurine supplementation to a cat with DCM due to taurine deficiency does not change the short-term prognosis. Cats that live longer than 2-3 weeks, however, almost all survive and their myocardial function normalizes over 3-5 months. Consequently, their long-term prognosis is excellent. In cats with DCM that is not due to taurine deficiency, the prognosis is usually grave. The median survival time on one study was only two weeks.
Plasma concentrations of amino acids
Plasma taurine concentration should be measured in any cat and any American cocker spaniel diagnosed to have DCM. This may also be true for golden retrievers, The blood should be drawn into a heparinized syringe or placed in a heparinized tube and placed on ice. Red cells and platelets concentrate taurine. Consequently, hemolysis and clot formation will markedly increase the concentration of taurine in plasma and must be avoided. Red cells will slowly leak taurine into plasma if the plasma is not separated from the red cells soon after collection. Consequently, the blood sample should be centrifuged within one hour of collection and the plasma harvested and placed in a separate tube. The plasma sample should be frozen until it is assayed. Some heparinized blood may also be saved to measure whole blood taurine concentration. A plasma taurine concentration <50 nmol/ml in dogs or cats is considered low. Most cats with DCM due to taurine deficiency have a plasma concentration < 20 nmol/ml. Dilated cardiomyopathy is rare in cats since the discovery that taurine deficiency causes DCM. In addition, of the cats identified with DCM, very few are taurine-deficient. Because taurine-induced feline DCM is reversible with supplementation, however, it must be ruled-out in each case.
Cats with DCM should be administered 250 mg taurine PO q12h until the results of the plasma analysis for taurine can be assessed or until a response to therapy can be assessed if plasma concentration is not measured. Echocardiographic response to therapy generally takes 2-4 months although clinical signs often start to improve within 3 weeks. If a cat is not taurine-deficient or it does not respond to supplementation, further taurine administration is not warranted.
©Mark D. Kittleson, D.V.M., Ph.D. All rights reserved.